Clinical trial capacity building in a pandemic-outcome of a rapid site readiness project in Latin America.

Background: Latin America (Latam) has a tradition of large-scale vaccine trials. Because of fluctuating demand, many sites have downsized their infrastructure. Therefore, BMGF launched a clinical trial site-readiness initiative early in the coronavirus-2019 (COVID-19) pandemic including Latam countries between August and September 2020. This survey evaluated clinical development performance measures pre/post initiative (September 2022). Results: 20/21 prequalified sites participated in COVID-19 vaccine/drug development trials. 156 clinical trials (140 COVID-19 vaccine/drug trials) were initiated in the 2 years since prequalification, compared to 176 in the 5 years before. 33,428/37,810 participants were included in COVID-19 programs. The number of enrolled subjects/day across sites quadrupled from 15 (1-35) to 63 (5-300). The dropout rate was 6.8%. Study approval timelines were reduced from 60 (12-120) to 35 (5-90) days. Mean qualified staff was increased from 24 (6-80) to 88 (22-180). Conclusion: Clinical trial sites across Latam were successfully prequalified to participate in COVID-19 developments. For the 100 days mission of vaccine availability in a new pandemic sufficient and well-trained clinical trial sites readily available are essential. This is only achievable if sites-especially in low/middle-income countries-are maintained active through a constant flow of vaccine studies.

Assessment of health care workers preparedness to epidemics: A case of Ebola virus disease preparedness in private hospitals in Kampala, Uganda.

INTRODUCTION: Unrecognized Ebola Virus Disease (EVD) can lead to multiple chains of transmissions if the first caretakers are not trained and prepared. This study aimed to assess healthcare workers (HCWs) preparedness in private hospitals located in Kampala, to detect, respond and prevent EVD. METHODOLOGY: A descriptive cross-sectional study was carried out among HCWs in direct clinical care provision in four private hospitals, and in one Ebola Treatment Unit (ETU) using a self-administered questionnaire from March to June 2020. RESULTS: 222 HCWs agreed to participate aged from 19 to 64 years and with 6 months to 38 years of practice where most were nurses (44%). 3/5 hospitals did not have written protocols on EVD case management, and only one (ETU) had an exclusive emergency team. 59% were not sure whether contact tracing was taking place. Private hospitals were not included in EVD trainings organized by the Ministry of Health (MoH). In addition, HCWs in private hospitals were not empowered by the MoH to take part in EVD case management. Despite these shortcomings, only 66% of HCWs showed an interest to be immunized. Knowledge about potential Ebola vaccines was generally poor. CONCLUSIONS: In Kampala, Uganda, establishment of a more comprehensive preparedness and response strategy for EVD outbreaks is imperative for HCWs in private facilities, including a wide vaccination educational program on Ebola vaccination. The findings from this study if addressed will likely improve the preparedness and management of future Ebola outbreaks in Uganda.

Novel Oral Polio Vaccine Type 2 Use for Polio Outbreak Response: A Global Effort for a Global Health Emergency.

A sharp rise in circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks in the years following the cessation of routine use of poliovirus type 2-containing oral polio vaccine and the trend of seeding new emergences with suboptimal vaccination response during the same time-period led to the accelerated development of the novel oral polio vaccine type 2 (nOPV2), a vaccine with enhanced genetic stability and lower likelihood of reversion to neuroparalytic variants compared to its Sabin counterpart. In November 2020, nOPV2 became the first vaccine to be granted an Emergency Use Listing (EUL) by the World Health Organization (WHO) Prequalification Team (PQT), allowing close to a billion doses to be used by countries within three years after its first rollout and leading to full licensure and WHO prequalification (PQ) in December 2023. The nOPV2 development process exemplifies how scientific advances and innovative tools can be applied to combat global health emergencies in an urgent and adaptive way, building on a collaborative effort among scientific, regulatory and implementation partners and policymakers across the globe.

Landscaping analysis of immunization progress and program structures in selected middle income Southeast Asian countries.

This study examined the performance and structures of national immunization program in five middle-income Southeast Asian countries - Malaysia, Thailand, Philippines, Viet Nam, and Myanmar, and analyzed how the different structures relate to the difference in program performance to identify effective strategies in the study countries that facilitated good immunization performance. Data were derived from published literature, and WHO/UNICEF/Gavi databases, with 2010 as the baseline year. UMICs Malaysia and Thailand maintained ≥90 % coverage from 2010 to 2020 and even during the COVID-19 pandemic in 2021. LMICs Viet Nam and donor-supported Myanmar also achieved 80-90 % coverage for most routine vaccines in 2020. The Philippines have not reached ≥90 % coverage since 2010, with the maximum only 72 % (MCV1 and Polio3) in 2020. All study countries prioritize immunization and increased government financing since 2010 by minimum 91 % in Malaysia and 1897 % in Myanmar. However, Myanmar still largely depended on donor support with government financing only 32 % of immunization costs in 2021. The Philippines funds 100 % of immunization costs and ensures sustainable financing for the NIP through earmarked "sin tax" revenues from alcohol and tobacco. Donor support influenced new vaccine introductions among the study countries, with Gavi countries Myanmar and Viet Nam introducing more new vaccines, compared to Gavi-ineligible Malaysia and Thailand. The Philippines reported vaccine stock-outs every year amounting to 28 stock-outs events from 2010 to 2019, compared to only 1-4 stockouts in the other study countries. Donor support, innovative financing, and domestic vaccine manufacturing all play an important role in the efficient delivery of immunization services as demonstrated by the several new vaccine introductions and high immunization rates in Myanmar though Gavi and UNICEF support, additional annual $1.2 billion budget for health and immunization from "sin taxes" in the Philippines, and lack of stockouts for vaccines sourced at affordable prices from domestic manufacturers in Viet Nam.

The need and challenges for development of vaccines against emerging infectious diseases

Abstract Objective: To identify and describe learnings from past pandemics and to suggest a framework for vaccine development as part of epi/pandemic readiness. Source of data: Articles/ reviews/letters on pandemic preparedness/ vaccines published between 2005 and 2022 in PubMed, MEDLINE, MedRxiv, BioRxiv, Research Square, Gates Open Research; who. int, cepi.net, visualcapitalist.com, airfinity.com, ted.com websites; press releases. Summary of findings: Disease pandemics caused by emerging pathogens impacted the social development, health and wealth of most societies in human history. In an outbreak, the first months determine its course. To block an exponential spread and the development of an epi/ pandemic early, vaccine availability in sufficient quantities is of paramount importance. It is inevitable that new human viruses will emerge. Any future pandemic will come likely from RNA viruses through zoonotic or vector transmission, but we cannot predict when or where "Disease X" will strike. Public health, scientific and societal readiness plans need to include: continuous identification of new viruses in common mammalian reservoir hosts; continuous epidemiological surveillance, including wastewater sampling; establishment of prototype vaccine libraries against various virus families sharing functional and structural properties; testing of various and innovative vaccine platforms including mRNA, vector, nasal or oral vaccines for suitability by virus family; functional clinical trial sites and laboratory networks in various geographies; more efficient phasing of preclinical and clinical activities; global harmonization and streamlining of regulatory requirements including pre-established protocols; and societal preparedness including combating any pandemic of misinformation. Conclusions: "Outbreaks are unavoidable, pandemics are optional".

Soroprevalência de anticorpos contra vírus herpes simples 1-2 no Brasil / Seroprevalencia de anticuerpos contra virus herpes simples 1-2 en Brasil / Seroprevalence of herpes simplex 1-2 antibodies in Brazil

OBJETIVO: Estimar a soroprevalência de anticorpos por vírus herpes simples (HSV-1 e HSV-2) e analisar fatores associados no Brasil. MÉTODOS: Estudo transversal realizado entre 1996 e 1997 em 1.090 indivíduos com idade entre um e 40 anos da população geral, em quatro diferentes regiões geográficas no Brasil. Foram analisadas amostras sangüíneas para detecção de anticorpos para HSV-1 e HSV-2 com teste tipo-específico Elisa. Foram descritas freqüências e proporções, comparadas entre grupos utilizando o teste de Fisher bilateral exato. Foi realizada análise de regressão logística para avaliar influência das variáveis sociodemográficas e histórico de DST, sobre a soroprevalência de HSV-1 e/ou HSV-2. RESULTADOS: As soroprevalências de anticorpos para HSV-1 e HSV-2, ajustadas por idade, foram 67,2 por cento e 11,3 por cento respectivamente, sem diferença quanto ao sexo e maiores na Região Norte...

OBJECTIVE: To estimate the seroprevalence of HSV-1 and HSV-2 antibodies in Brazil and to analyze factors associated. METHODS: Cross-sectional study including subjects aged 1-40 years from the general population in four different geographical areas in Brazil between 1996 and 1997. All subjects were stratified by age and gender and 1,090 of them were included in the final analysis. Blood samples were tested for HSV-1 and HSV-2 antibodies by type-specific (gG1 and gG2) ELISA. Frequencies and proportions were described and compared among groups using two-sided Fisher's exact test. A logistic regression analysis was performed to assess the influence of the variables age, gender, geographical area, socioeconomic condition, past history of STD, seropositivity for anti-HSV-1 or anti-HSV-2 and interactions of any of these factors on the seroprevalence of HSV-1 and/or HSV-2. RESULTS: The age-adjusted seroprevalences of HSV-1 and HSV-2 antibodies were 67.2 percent and 11.3 percent, respectively, without sex differences and being higher in the North region...

OBJETIVO: Estimar la seroprevalencia de anticuerpos por virus herpes simples (HSV-1 y HSV-2) en diferentes áreas geográficas en Brasil y analizar factores asociados. MÉTODOS: Estudio transversal realizado entre 1996 y 1997 con individuos de la población en general en cuatro diferentes áreas geográficas en Brasil y estratificados por edad (de uno a 40 años) y sexo, de los cuales 1.090 fueron incluidos en el análisis final. Fueron analizadas muestras de sangre para detección de anticuerpos para HSV-1 y HSV-2 con prueba tipo-específica ELISA gG1-gG2. Fueron descritas frecuencias y proporciones y comparadas entre grupos utilizando la prueba de Fisher bilateral exacta. Fue realizado análisis de regresión logística para evaluar influencia de las variables edad, sexo, geografía, grupo económico, histórico de DST, seropositividad para anti-HSV-1 o anti-HSV-2 e interacciones de cualquiera de esos factores sobre la seroprevalencia de HSV-1 y/o HSV-2. RESULTADOS: La tasa de seroprevalencia de anticuerpos para HSV-1 ajustada por edad fue de 67,2 por ciento, sin diferencia con relación al sexo, siendo mayor en la Región Norte...

Estudo de soroprevalência de anticorpos contra os vírus herpes simples 1 e 2 no Brasil / Herpes simplex virus type 1 and type 2 seroprevalence study in Brazil

Objetivo: Determinar a soroprevalência de anticorpos para HSV-1 e HSV-2, por faixa etária e sexo, em indivíduos entre 1 e 40 anos no Brasil e analisar a influência de fatores socioeconômicos, doenças sexualmente transmissíveis e da infecção pregressa por herpes simples nas prevalências de anticorpos para HSV-1 e HSV-2. Métodos: Entre abril de 1996 e maio de 1997, recrutaram-se 1.320 indivíduos, de quatro regiões do Brasil, estratificando-os por idade e sexo. Amostras sanguíneas para detecção de anticorpos para HSV-1 e HSV-2 foram analisadas usando-se o teste tipo-específico ELlSA gG1-gG2. Resultados: Dos 1.320 indivíduos, 1.090 foram aceitos na análise. A taxa global da soroprevalência de anticorpos para HSV-1 foi de 70,8 por cento (95 por cento IC: 68,0 73,5), sem diferença quanto ao sexo; 25 por cento dos participantes tornaram-se soro positivos para HSV-1 aos 4 anos, 50 por cento aos 7 anos e 75 por cento aos 24 anos de idade. A soroprevalência de anticorpos para HSV-1 não está relacionada à condição socioeconômica, doença sexualmente transmissível ou infecção pregressa por HSV-2. I Tal soroprevalência, ajustada por idade, foi maior na região Sudeste. A prevalência global de anticorpos para HSV-2 foi de 12,5 por cento (95 por cento IC: 10,6-14,6), similar para ambos os sexos. Somente 2,2 por cento dos soropositivos para HSV-2 relataram ocorrência pregressa de herpes genital. A soroprevalência para HSV-2 foi influenciada principalmente pela idade, aumentando de 1 por cento, em adolescentes, para 25 por cento entre adultos jovens. A taxa de infecção para HSV-2, ajustada por faixa etária, foi maior na região Norte. Indivíduos soro positivos para HSV-1 denotavam maior possibilidade de também serem positivos para HSV-2 quando comparados com os negativos para HSV-1: 15,7 por cento contra 4,7 por cento. O histórico de doenças sexualmente transmissíveis aumentou a possibilidade de soropositividade para HSV-2, na análise multivariada, em 3,2 vezes, enquanto que a condição socioeconômica não influenciou a soroprevalência de anticorpos para HSV-2. Conclusões: O Brasil é considerado um país de elevada endemicidade para HSV-1, com taxas expressivas de infecção em idade muito jovem, sugerindo a via de transmissão oral. As infecções por HSV-2, por sua vez, são transmitidas predominantemente via sexual. A história médica mostrou-se inadequada com vistas a identificar pacientes positivos para HSV-2, subestimando-se, pois, a magnitude da epidemiologia da infecção por HSV-2 no Brasil.

Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine / Vacunación primaria y de refuerzo con la vacuna pentavalente DTPw-HB/Hib en niños costarricenses vacunados al nacer contra la hepatitis B

Objective. The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B (HB) and Haemophilus influenzae type b (Hib) vaccines into routine childhood vaccination programs. The objectives of this study were to: 1) analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2) in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster. Methods. In the first part of the study (primary-vaccination stage), conducted in 1998-1999, we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2, 4, and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth. Later, in the booster-vaccination stage of the study, in 1999-2000, in a subset of the children (69 toddlers, now 15-18 months old), antibody persistence was measured, and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed. Results. In both primary-vaccination groups, at least 97.5 percent of the infants reached protective levels of antibodies (seropositivity) against the antigens employed in the vaccines. The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone, and, in terms of general reactions, there was no clinically significant difference between the combination or separate injections, and with the pentavalent vaccine having the benefit of needing one less injection. Nine months after the third dose of the primary-vaccination course, antibody persistence was similar in both groups, with over 93 percent of children still having protective/seropositive titers for Hib, HB, and tetanus and about 50 percent for diphtheria and Bordetella pertussis. At 15 months of age, virtually all the toddlers responded with a strong boost response to all the vaccine antigens, whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster. Both booster regimens were equally well tolerated, indicating that up to five...

Traveler's diarrhea: epidemiology and impact on visitors to Fortaleza, Brazil / La diarrea del viajero: su epidemiología e impacto en turistas que visitan Fortaleza, Brasil

Objective. To assess the epidemiology and impact of traveler's diarrhea (TD) among visitors to the city of Fortaleza, Ceará, Brazil, as part of a global study on TD carried out in four countries. Methods. Within a cross-sectional survey, questionnaires were completed by departing questions inquired about demographics, duration of stay, reason for their visit, pretravel health advice they had received, risky food and beverage consumption while in Fortaleza, and quality of life during the visit to Fortaleza in relation to having or not having contracted TD. Results. A total of 12 499 questionnaires were analyzed. The most common reason that the visitors gave for their travel to Fortaleza was a holiday (60.3%). The total diarrhea attack rate was 13.4%. Younger people (< 36 years) had significantly higher TD attack rates than did older persons. Using a logistic regression model, we investigated the visitors' risk factors, including age, gender, length of stay, and trip's purpose. According to that analysis, characteristics that are slightly predictive of TD are gender, length of stay, and visiting as a tourist rather than for some other purpose. Characteristics that protect against contracting TD include being older and traveling for business rather than for some other reason. Of those who were incapacitated by TD, the mean duration of the impairment was 42 hours. Conclusions. TD affected the travel plans and activities of many of the visitors to Fortaleza. Further, although aware of the health risks, the majority of those travelers did not avoid all potentially contaminated food or beverage items. Given this pattern of behavior, future efforts to combat TD may have to depend on such other alternative strategies as new vaccines

Objetivo. Evaluar la epidemiología y el impacto de la diarrea del viajero (DV) en personas que visitan Fortaleza, Brasil, como parte de un estudio general sobre la DV efectuado en cuatro países. Métodos. Se realizó una encuesta transversal en la que se pidió a personas en el aeropuerto que salían de Fortaleza entre marzo de 1997 y febrero de 1998 que completaran un cuestionario. Había preguntas sobre sus características demográficas, la duración de su estancia, la razón de la visita, los consejos que habían recibido antes del viaje, el consumo de alimentos y bebidas peligrosas en Fortaleza, y la calidad de vida durante su visita en relación con la presencia o ausencia de DV. Resultados. Se examinó un total de 12 499 cuestionarios. La razón citada con mayor frecuencia para haber viajado a Fortaleza fue tomarse vacaciones (60,3%). La tasa de ataque global fue de 13,4%. Las personas más jóvenes (< 36 años) tuvieron tasas de ataque mucho más altas que las de edad más avanzada. Usamos un modelo de regresión logística para investigar los factores de riesgo que tenían los turistas, entre ellos la edad, el sexo, la duración de la estancia y el motivo del viaje. Según los resultados de ese análisis, las características que predicen levemente la aparición de DV son el sexo, la duración de la estancia y el estar en viaje de turismo y no de cualquier otro tipo. Ser una persona de mayor edad y haber viajado por razones de negocio en lugar de otros motivos son factores que protegen contra la DV. De las personas que sufrieron discapacitación debido a la DV, la duración media del trastorno fue de 42 horas. Conclusiones. La VD afectó a los planes y actividades de turismo de muchas de las personas que visitaron Fortaleza. Aunque sabían que corrían un riesgo, la mayoría de esos viajeros no se abstuvieron de consumir alimentos o bebidas que podían estar contaminados. En vista de que así se comportan los viajeros, en un futuro cualquier iniciativa orientada a combatir la DV deberá depender de estrategias de otra índole, como por ejemplo, la aplicación de una nueva vacuna